Objective：To evaluate the effect of fatty liver induced by high fat diet in C57 mice on bone microstructures and the possible mechanism. Methods：A total of 20 C57 male mice（4 weeks old）were enrolled and divided into two groups，fed for 12 weeks either with standard chow（control；n=9）or with high-fat diet to induce fatty liver（HFD；n=11）. Blood，femur，tibia and liver samples were collected after sacrifice. Plasma alanine aminotransferase（ALT）and aspartate aminotransferase（AST）concentration were examined. The liver was stained with H&E and Oil red-O to determine if the mice were suffering from fatty liver and to measure the amount of triglyceride（TG）and total cholesterol（TC）. The bone samples were scanned using a micro-CT system in a high-resolution scanning mode. Total volume（TV），bone volume（BV），total bone volume fraction（BV/TV），connectivity density（Conn.D），structural model index（SMI），trabecular number（Tb.N），trabecular thickness（Tb.Th），trabecular spacing（Tb. Sp），apparent density（Ap.Dens），material density（Mat.Dens）and degree of anisotropy（DA）were compared between control and HFD groups. The number of marrow fat drops was measured by some of the femur with HE staining. Results：In the HFD group，all mice were proved with fatty liver by liver H&E and oil red O staining. Compared to the control group，the HFD group had lower levels of TV［（2.128 ± 0.591）mm3 vs.（3.570 ± 0.330）mm3，P < 0.001）］，Tb.N［（1.769 ± 0.218）/mm vs.（2.284 ± 0.726）/mm，P=0.030）］，SMI（2.950 ± 0.242 vs. 3.820 ± 0.729，P=0.004）and higher levels of Tb.Sp［（0.595 ± 0.083）mm vs.（0.472 ± 0.116）mm，P=0.013］in femur. The HFD group also had lower levels of TV［（1.127 ± 0.338）mm3 vs.（1.741±0.683）mm3，P=0.017］and SMI（2.431 ± 0.501 vs. 3.188 ± 0.465，P=0.003）in tibia. Bone marrow histomorphological analysis showed that the number of adipose drop（AD）per mm2 bone marrow was significantly higher in the HFD group compared with control mice（5.5 ± 2.2 vs. 2.6 ± 0.5，P=0.042）. AD was positively with TV（Femur：r= -0.756，P=0.030；Tibia：r= -0.771，P=0.025）. Conclusion：Our results suggest an adverse effect of fatty liver on bone microstructure in C57 mice. Bone marrow adiposity may be a factor underlying this physiopathologic process.